Kidney disease is an alarming universal health concern and a leading cause of morbidity and mortality. About 861 million individuals around the world suffer from kidney complications. However, current treatment alternatives are limited. These limitations underscore the urgent need for new therapeutic approaches. Autophagy is a dynamic and cellular housekeeping mechanism. The use of conditional autophagy-related gene knockouts in kidney cells has led to a better understanding of autophagy’s significance. Basal autophagy in the kidney serves as a quality control mechanism, vital for cellular metabolism and organelle homeostasis. Under stressful conditions, kidney cells adapt their autophagic activity. This process is intricately controlled by signaling pathways that control autophagic flux, with sirtuins, AMP-activated protein kinase (AMPK), and mammalian target of rapamycin (mTOR) acting as key regulators. Additionally, autophagy plays a role in the natural aging process of renal tissue. Small-molecule natural products have demonstrated efficacy in regulating autophagy and mitigating kidney damage in several experimental studies. However, specific mechanisms by which small molecules regulate autophagy across different renal disorders have yet to be fully understood. This study shows that the recent advancements in using small molecules in autophagy research have reignited interest in the related signaling pathways and their role in the pathophysiology of renal diseases. Further research on autophagy and its regulatory signaling networks could provide new therapeutic targets for small-molecule intervention in renal disorders.

Kidney disease is an alarming universal health concern and a leading cause of morbidity and mortality. About 861 million individuals around the world suffer from kidney complications. However, current treatment alternatives are limited. These limi-tations underscore the impending need for new therapeutic approaches. Autophagy is a dynamic and cellular housekeeping mechanism. The use of conditional autopha-gy-related gene knockouts in kidney cells has led to a better understanding of au-tophagy's significance. Basal autophagy in the kidney serves as a quality control mechanism, vital for cellular metabolism and organelle homeostasis. Under stressful conditions, kidney cells adapt their autophagic activity. This process is intricately con-trolled by signalling pathways that control autophagic flux, with sirtuins, AMP-activated protein kinase (AMPK), and mammalian target of rapamycin (mTOR) acting as key regulators. Additionally, autophagy plays a role in the natural aging process of renal tissue. Small-molecule natural products have demonstrated efficacy in regulating au-tophagy and mitigating kidney damage in several experimental studies. However, specific mechanisms by which small molecules regulate autophagy across different renal disorders have yet to be fully understood. This study reviews that the recent advance-ments in using small molecules in autophagy research have reignited interest in the related signalling pathways and their role in the pathophysiology of renal diseases. Further research into autophagy and its regulatory signalling networks could provide new therapeutic targets for small-molecule intervention in renal disorders.